Hammers Dustin B, Eloyan Ani, Taurone Alexander, Thangarajah Maryanne, Gao Sujuan, Beckett Laurel, Polsinelli Angelina J, Kirby Kala, Dage Jeffrey L, Nudelman Kelly, Aisen Paul, Reman Rema, La Joie Renaud, Lagarde Julien, Atri Alireza, Clark David, Day Gregory S, Duara Ranjan, Graff-Radford Neill R, Grant Ian, Honig Lawrence S, Johnson Erik C B, Jones David T, Masdeu Joseph C, Mendez Mario F, Womack Kyle, Musiek Erik, Onyike Chiadi U, Riddle Meghan, Rogalski Emily, Salloway Steven, Sha Sharon J, Turner Raymond Scott, Wingo Thomas S, Wolk David A, Carrillo Maria C, Rabinovici Gil D, Dickerson Bradford C, Apostolova Liana G
Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, Rhode Island, USA.
Alzheimers Dement. 2025 Feb;21(2):e14439. doi: 10.1002/alz.14439. Epub 2024 Dec 23.
Early-onset Alzheimer's disease (EOAD) manifests prior to the age of 65, and affects 4%-8% of patients with Alzheimer's disease (AD). The current analyses sought to examine longitudinal cognitive trajectories of participants with early-onset dementia.
Data from 307 cognitively normal (CN) volunteer participants and those with amyloid-positive EOAD or amyloid-negative cognitive impairment (EOnonAD) were compared. Cognitive trajectories across a comprehensive cognitive battery spanning 42 months were examined using mixed-effects modeling.
The EOAD group displayed worse cognition at baseline relative to EOnonAD and CN groups, and more aggressive declines in cognition over time. The largest effects were observed on measures of executive functioning domains, while memory declines were blunted in EOAD.
EOAD declined 2-4× faster than EOnonAD, and EOAD pathology is not restricted to memory networks. Early identification of deficits is critical to ensure that individuals with sporadic EOAD can be considered for treatment using disease-modifying medications.
Represents the most comprehensive longitudinal characterization of sporadic EOAD to date. The trajectory of cognitive declines was steep for EOAD participants and worse than for other groups. Executive functioning measures exhibited the greatest declines over time in EOAD.
早发性阿尔茨海默病（EOAD）在65岁之前出现，影响4%-8%的阿尔茨海默病（AD）患者。当前分析旨在研究早发性痴呆症参与者的纵向认知轨迹。
比较了307名认知正常（CN）志愿者参与者以及淀粉样蛋白阳性EOAD或淀粉样蛋白阴性认知障碍（EOnonAD）患者的数据。使用混合效应模型检查了在42个月内跨越综合认知测试组合的认知轨迹。
与EOnonAD和CN组相比，EOAD组在基线时认知较差，且随着时间推移认知下降更明显。在执行功能领域的测量中观察到最大影响，而EOAD中的记忆下降则不那么明显。
EOAD的下降速度比EOnonAD快2-4倍，且EOAD病理不限于记忆网络。早期识别缺陷对于确保散发性EOAD患者能够考虑使用疾病修饰药物进行治疗至关重要。
代表了迄今为止对散发性EOAD最全面的纵向特征描述。EOAD参与者的认知下降轨迹很陡，且比其他组更差。随着时间推移，执行功能测量在EOAD中下降最大。
